An estimated 2.5 billion humans experience iron deficiency anemia. When this occurs during early development, there are significant alterations in behavior and cognition. The purpose of this rodent project is to broadly characterize the behavioral alterations related to early iron deficiency and the effects on several aspects of brain function. We propose two studies that vary in the degree of anemia (severe or moderate), but assess similar periods of iron deficiency (primarily myelin development, and both). These periods were chosen to provide close developmental links to the human and primate projects in this program. Behavioral and neurobiologic measures will be assessed at several ages before weaning and into adulthood with n=16-32 litters per group. Specific Aims 1-3 will be assessed in both studies using the same animals. Aim 4 will be assessed in separate experiments using the severe level of iron deficiency. Each aim will assess the effect of iron deficiency during early development on: measures of sensorimotor skill emergence, affect-related behaviors, and cognition (Aim 1); measures of dopamine metabolism (DA transporter, D1, D2, and D2-like receptor densities; DA, DA metabolites, tyrosine hydroxylase), in situ hybridization of mRNAs for these proteins and other neurotransmitters systems (serotonin and norepinephrine) (Aim 2); measures of oligodendrocyte and myelin development (Tf mRNA using in situ hybridization; content of lipid, cholesterol and galactolipids) (Aim 3); and measures of brain energy metabolism using MRS (lactate, glucose, NAA, Cr/PCr, TCA cycle activity and glucose exchange across the mitochondrial membrane), and regional CytOx activity (Aim 4). We expect that alterations in behavioral and neurobiologic outcomes will depend on the timing, severity and duration of iron deficiency during development. We anticipate that the findings from this project will assist the interpretation of measures in other projects in this program and the generation of hypotheses regarding the relationship of neurobiologic alterations and functional behavioral changes with developmental iron deficiency.